We propose a comprehensive investigation of the regulation by insulin and glucagon of fatty acid and cholesterol synthesis in mammalian liver. In addition, we hope to be able, in the course of this investigation, to identify the biochemical defects that exist in the regulation of the synthesis of these compounds in the diabetic animal. Specific problems in this investigation will concern the mechanism by which insulin and glucagon regulate (1) short-term changes in fatty acid synthesis, (2) the rate of synthesis and the content in liver of fatty acid synthetase, malic enzyme and acetyl-CoA carboxylase, (3) the interconversion of enzymatically active and inactive species of beta-hydroxy-beta-methylglutaryl coenzyme A reductase and (4) changes in the rate of synthesis and quantity of this enzyme in liver. As part of these investigations we expect to isolate and purify enzymes that effect an interconversion of enzymatically active and inactive species of lipogenic enzymes. We also expect to isolate and purify mRNAs for fatty acid synthetase, malic enzyme and acetyl-CoA carboxylase. These studies will then lead to a thorough investigation of the identity of the products formed when these mRNAs are translated in cell-free protein synthesizing systems.